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RESEARCH PRODUCT

Clinical Characteristics of Patients Carrying the Q703K Variant of the NLRP3 Gene: A 10-year Multicentric National Study

Alberto TommasiniSonia CartaL CantariniOrso Maria LucheriniAnna RubartelliMarco CimminoFederica PencoAntonella InsalacoMariolina AlessioFrancesco CaroliA NaselliAlberto MartiniLaura ObiciIsabella CeccheriniMarco GattornoRomina GalliziCristina MaggioSara Signa

subject

0301 basic medicineMalePathologyMonocyteGastroenterologyMonocytesInflammasome0302 clinical medicineCRYOPYRIN-ASSOCIATED PERIODIC SYNDROMEImmunology and AllergyYoung adultChildeducation.field_of_studyCRYOPYRINMiddle AgedInterleukin-1βPhenotypeArthralgiaPhenotypeChild PreschoolNational studyCytokinesFemaleHumanAdultCryopyrinmedicine.medical_specialtyAdolescentImmunologyPopulationNLR Family03 medical and health sciencesYoung AdultRheumatologyNLRP3Internal medicineNLR Family Pyrin Domain-Containing 3 ProteinmedicineHumansPreschooleducationCytokineAllele frequencyGene030203 arthritis & rheumatologybusiness.industryCryopyrin-associated periodic syndromeInfantExanthemamedicine.diseasePyrin Domain-Containing 3 ProteinCryopyrin-Associated Periodic SyndromesINTERLEUKIN-1βCryopyrin-Associated Periodic Syndrome030104 developmental biologyINFLAMMASOMEMutationCryopyrin; Cryopyrin-Associated Periodic Syndrome; Inflammasome; Interleukin-1β; NLRP3; Adolescent; Adult; Arthralgia; Child; Child Preschool; Cryopyrin-Associated Periodic Syndromes; Cytokines; Exanthema; Female; Humans; Infant; Male; Middle Aged; Monocytes; NLR Family Pyrin Domain-Containing 3 Protein; Young Adult; Mutation; PhenotypeCytokine secretionbusinessCRYOPYRIN; CRYOPYRIN-ASSOCIATED PERIODIC SYNDROME; INFLAMMASOME; INTERLEUKIN-1β; NLRP3

description

Objective.The aim of our study was to analyze the clinical and functional effect of the p.Q703K (p. Q705K, c. 2107C>A) variant of the NLRP3 gene in a population of patients screened for suspected cryopyrin-associated periodic syndrome (CAPS).Methods.Since 2002, 580 patients underwent molecular analysis for NLRP3. Data on clinical presentation, response to treatment, and longterm followup were collected using a uniform questionnaire. The pattern of cytokine secretion after lipopolysaccharide stimulation from isolated monocytes was analyzed in 3 patients carrying the p.Q703K variant and 1 patient with a chronic infantile neurologic, cutaneous, articular syndrome phenotype carrying both the p.M406I and p.Q703K, and compared with 7 patients with CAPS with sure pathogenic variants and 6 healthy controls.Results.The p.Q703K variant was found in 57 screened patients with an overall allelic frequency of 5%. The frequency in normal controls was 5.5%. Clinical data at the moment of molecular analysis and at followup were available in 36 patients. Two patients displayed additional mutations of NLRP3. The mean followup was 2.5 years. Thirteen patients (39%) had a final diagnosis different from the original suspicion of CAPS. The remaining 21 patients displayed a mild phenotype mainly characterized by recurrent episodes of urticarial rash and arthralgia. Only 8 patients were treated with anti-interleukin (IL)-1 treatment, with a complete response in 5 patients. The pattern of secretion of IL-1β and other cytokines (IL-6 and IL-1 receptor antagonist) in patients did not display the aberrancies observed in patients with CAPS and was similar to that observed in healthy controls.Conclusion.The present study confirms the weak clinical and functional effect of the p.Q703K variant.

yearjournalcountryeditionlanguage
2016-01-01
10.3899/jrheum.150962http://hdl.handle.net/11365/997905